Multiple transcriptomic comprehensive analyses highlight key genes and cast new light on multifaceted pathways that may be important arenas in rice innate immunity against Magnoporthe oryzae blast disease. Magnaporthe oryzae (MOR) poses a significant threat to rice production worldwide. However, defense mechanisms in rice against MOR remain inadequately defined. In this study, a multi-transcriptomic integrative analysis on 441 samples from diverse microarrays and RNA-seq sets was conducted to reveal critical factors in rice defense against MOR infection. A robust pattern of 3534 upregulated genes and 2920 repressed genes was commonly identified across all MOR-infected arrays and RNA-seq profiles. Interestingly, enrichment analysis revealed a consistent triggering of endoplasmic reticulum (ER)-related mechanisms and citric acid cycle (TCA) influx in rice response to MOR infection across all the transcriptome profiles, suggesting their critical role in modulating rice immunity against the pathogen. By contrast, chloroplast and photosynthesis pathways were frequently repressed across all the profiles. Among ER-related mechanisms, the phagosome pathway involved in the activation of NADPH oxidase was highly triggered in early response to MOR infection. Moreover, WGCNA analysis highlighted four key co-expressed gene modules and 80 significant hub genes associated with MOR infection. Among the core genes, Sec61 gene involved in the ER-translocation process was identified along with OsMFP (peroxisomal oxidation gene) and OSAHH gene (involved in cyclic-trans-methylation). Furthermore, MPK6, WRKY24, NUP35, and NPR1 genes were observed as core co-expressed genes, suggesting their significance in regulating rice immunity against MOR. Our findings elucidate key genes and multifaceted mechanisms in rice-MOR interaction, proposing new informative clues that can be exploited to improve rice resistance against blast disease.